In the 25 years of cancer prevention research, few interventions have been identified that have effects on more than one type of cancer. Chronic inflammation contributes to carcinogenesis in multiple organs, thus anti-inflammatory agents have the potential to reduce the risk of cancer at several sites. In 1999, Dr. Emily White was awarded funding for the VITamins And Lifestyle (VITAL) study, a prospective cohort study of dietary supplement use and cancer risk. 77,738 men and women in western Washington State, age 50-76, entered the cohort, by completing a detailed questionnaire on use of 38 supplements over the past 10 years, diet, and lifestyle factors. Over 54,000 participants also provided buccal cell specimens for DNA. The strongest and most consistent findings to date are that only the anti-inflammatory supplements (in particular glucosamine, chondroitin and fish oil/n-3 fatty acids) appear to reduce the risk of several cancers. This proposed Established Investigator Award (K05) for Dr. White would provide protected time for mentoring and research in the area of anti-inflammatory exposures and cancer risk, and other topics of interest to her trainees. The applicant has an extensive history of mentoring and directing training programs, is currently mentoring 1 pre-doctoral, 4 post-doctoral and 7 junior faculty members from a range of fields, and has a strong commitment to continue mentoring in the future. The availability of the data and specimens from the large VITAL cohort, the increasing numbers of cancers as the study matures (over 10,300 cancers expected by 2011), and the range of cancers that can be studied (prostate, breast, lung, colorectal, melanoma, bladder, blood/lymph) attract young investigators to work with her. In addition to providing ideas, guidance and the research platform for publishing research papers to her trainees, the applicant endeavors to provide guidance in developing their independent research as well. This award would provide additional time for Dr. White to expand her and her trainees'research to other anti-inflammatory supplements (e.g., grapeseed, MSM) which have not been ascertained by other cohorts, to anti-inflammatory drugs, and to pro- and anti-inflammatory dietary factors (e.g., n-6 and n-3 polyunsaturated fatty acids) in relation to incidence of multiple types of cancer, total cancer incidence and cancer mortality. In addition, the award would provide pilot data to allow her and her trainees to branch out into short-term randomized trials of the effects of potential chemopreventive agents on biomarkers of inflammation, and to studies of the anti-inflammatory exposures of interest and survival from cancer. Dr. White is also author of the book "Principles of Exposure Measurement in Epidemiology", and this award would provide dedicated time for her to pursue additional methodologic research in this area. To accomplish this, the applicant will reduce her large administrative responsibilities, including stepping down from her role as Associate Dean for Research in the University of Washington School of Public Health. PUBLIC HEALTH RELEVANCE: The proposed studies would provide information to help guide the American public about the benefits and risks of taking certain anti-inflammatory supplements. In addition, if any observed protective associations of anti-inflammatory supplements or anti-inflammatory dietary factors with cancer risk are found to be of reasonable magnitude, then they may deserve further investigation as cancer prevention interventions. This award would also provide training to young epidemiologists, nutrition scientists and physician-researchers who will become the next generation of cancer prevention scientists.